This proposal examines the hypothesis that norepinephrine and related phenylethylamines (isoproterenol, epinephrine, etc.) can interact with a functional inhibitory site in isolated guinea-pig ileum distinct from currently defined alpha- and beta- adrenoceptors. The research objective is to characterize this putative adrenoceptor with regard to agonist and antagonist profiles. Quantitative pharmacological experiments are planned to measure pA2 values for competitive antagonists, the sensitivity of the putative site to irreversible antagonists, and agonist potency ratios, affinities, and efficacies. Characterization of the putative adrenoceptor in isolated guinea- pig ileum will lead to similar experimentation in isolated guinea- pig atria, rat atria, rabbit rectococcygeus muscle, rat stomach fundus, and rat vas deferens. (Evidence exists that an adrenoceptor, distinct from defined alpha- and beta-subtypes, exists in these tissues). The research project represents a basic science, pharmacological approach, to effector receptor classification and characterization. The results may have relevance to both physiological mechanisms and novel drug development.